Devices and methods for control of blood pressure

ABSTRACT

Apparatus and methods are described including an implantable device shaped to define (a) at least two artery-contact regions, the artery-contact regions comprising struts that are configured to stretch an arterial wall by applying pressure to the arterial wall, and (b) at least two crimping regions that comprise locking mechanisms configured to prevent the crimping regions from becoming crimped due to pressure from the wall of the artery on the artery-contact regions. The crimping regions are configured to be crimped during insertion of the device, via a catheter, by the locking mechanisms being unlocked during insertion of the device. Other embodiments are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present patent application is a divisional of U.S. patentapplication Ser. No. 13/030,384, filed Feb. 18, 2011, now U.S. Pat. No.9,125,732, issued Sep. 8, 2015, which is a continuation-in-part of U.S.patent application Ser. No. 12/774,254, filed May 5, 2010, which is acontinuation-in-part of U.S. patent application Ser. No. 12/602,787,filed May 17, 2011, now U.S. Pat. No. 9,125,567, issued Sep. 8, 2015,which is the U.S. national phase of PCT Application No.PCT/IL2009/000932 to Gross et al. (WO10/035271), filed Sep. 29, 2009,which claims priority from U.S. Provisional Patent Application Ser. No.61/194,339, filed Sep. 26, 2008, entitled “Devices and methods forcontrol of blood pressure”, the entire disclosures of which areincorporated herein by reference.

The present patent application is related to U.S. patent applicationSer. No. 11/881,256 (US 2008/0033501), filed Jul. 25, 2007, entitled“Elliptical element for blood pressure reduction,” which is acontinuation-in-part of PCT Application No. PCT/IL2006/000856 to Gross(WO 07/013065), filed Jul. 25, 2006, entitled, “Electrical stimulationof blood vessels,” which claims the benefit of (a) U.S. ProvisionalApplication 60/702,491, filed Jul. 25, 2005, entitled, “Electricalstimulation of blood vessels,” and (b) U.S. Provisional Application60/721,728, filed Sep. 28, 2005, entitled, “Electrical stimulation ofblood vessels.”

All of the above applications are incorporated herein by reference.

FIELD OF EMBODIMENTS OF THE INVENTION

Some applications of the present invention generally relate to implantedmedical apparatus. Specifically, some applications of the presentinvention relate to apparatus and methods for reducing blood pressure.

BACKGROUND

Hypertension is a condition from which many people suffer. It is aconstant state of elevated blood pressure which can be caused by anumber of factors, for example, genetics, obesity or diet. Baroreceptorslocated in the walls of blood vessels act to regulate blood pressure.They do so by sending information to the central nervous system (CNS)regarding the extent to which the blood vessel walls are stretched bythe pressure of the blood flowing therethrough. In response to thesesignals, the CNS adjusts certain parameters so as to maintain a stableblood pressure.

SUMMARY OF EMBODIMENTS

For some applications, a subject's hypertension is treated by modulatingthe subject's baroreceptor activity. Mechanical and other forces areapplied directly or indirectly to one or more of the subject's arteriesin order to modulate the baroreceptor response to the blood pressure.The forces are typically applied to arteries that are rich inbaroreceptors, for example, the carotid arteries, the aorta, thesubclavian arteries and/or arteries of the brain. For some applications,the forces are applied to other regions of the body that containbaroreceptors, such as the atria, the renal arteries, or veins.

Baroreceptors measure strain, which, in the case of a circular vessel,depends on the pressure and the radius of the vessel. As pressureincreases, the stress exerted on the wall increases, thereby increasingthe strain in the vessel wall. Equation 1 relates the wall stress σ in athin walled tube, to internal pressure p, internal radius r, and wallthickness t.σ=pr/2t  [Equation 1]

In a hypertensive patient, the pressure-strain relationship is typicallyshifted to higher pressures, such that the artery is subject to a givenstrain at a higher blood pressure than the blood pressure in a healthyvessel that would give rise to the given strain. Thus, the baroreceptorsare activated at a higher blood pressure in a hypertensive patient thanthey are in a healthy patient. The devices described herein typicallycause the pressure-strain curve to shift back to lower pressures.

The inventors hypothesize that, at constant pressure, by increasing theradius of curvature of a region of an arterial wall, the strain in theregion of the wall may be increased. Thus, the baroreceptor nerveendings in the region (which are typically disposed between the medialand adventitial layers of the artery, as described in further detailhereinbelow) experience greater strain, ceteris paribus. Theintravascular devices described herein typically increase the radius ofcurvature of regions of the arterial wall, but do not cause asubstantial decrease in the cross-section of the artery (and, typically,cause an increase in the cross-section of the artery), therebymaintaining blood flow through the artery. For some applications, thedevices change the shape of the artery such that the artery is lesscircular than in the absence of the device, thereby increasing theradius of curvature of sections of the arterial wall.

Typically, the devices described herein change the shape of the arteryby being placed inside or outside the artery, but by maintaining lessthan 360 degrees of contact with the surface of the artery at any givensite along the length of the artery. Further typically, contact betweenthe device and the artery is limited to several (e.g., two to six, orthree to six) contact regions around the circumference of the artery,and is generally minimized. Still further typically, the device isplaced inside the artery such that there are several regions at whichthe device does not contact the artery, each of the non-contact regionsbeing contiguous, and defining an angle that is greater than 10 degreesaround the longitudinal axis of the artery, as described in furtherdetail hereinbelow. This may be beneficial for the following reasons:

(1) A greater area of the artery pulsates in response to pressurechanges than if the device were to maintain a greater degree of contactwith the vessel wall. It is generally desirable to allow at least aportion of the vessel to pulsate freely. This is because pulsation ofthe vessel over the course of the cardiac cycle typically activates andmaintains normal functioning of the baroreceptors. For someapplications, baroreceptor activity in the portions of the vessel thatare in contact with the device may be reduced, since the movement ofthose portions in response to changes in blood pressure is reduced.Therefore, for some applications, contact between the device and theartery is minimized.

(2) A smaller metal to lumen ratio typically causes less reactive growthof endothelial and smooth muscle cells. Typically, reducing thisreactive growth reduces the chances of stenosis being caused by thedevice. Further typically, reducing this reactive growth facilitatesexplantation, and/or movement of the device, when desired.

For some applications the devices described herein are implantedtemporarily, and are subsequently removed. For example, one of thedevices described herein may be implanted for a period of less than onemonth, e.g., less than one week. Temporary implantation of the devicesis typically used to treat an acute condition of the subject. For someapplications, the shape of the artery in which the device is implantedis permanently altered by temporarily implanting the device.

Typically, the devices described herein are implanted inside or outsideof the subject's carotid artery, e.g., at the carotid sinus. Inaccordance with respective embodiments, the devices are implantedbilaterally, or inside or outside of only one of the subject's carotidarteries. Alternatively or additionally, the devices are placed insideor outside of a different artery, e.g., the aorta or the pulmonaryartery.

The devices are typically self-anchoring and structurally stable.Further typically, the devices are passive devices, i.e., subsequent tothe devices being implanted inside or outside of the artery, the devicesact to increase baroreceptor sensitivity without requiring electrical orreal-time mechanical activation.

There is therefore provided, in accordance with some applications of thepresent invention, a method, including:

identifying a subject as suffering from hypertension; and

in response to the identifying,

-   -   (a) increasing a radius of curvature of a first set of at least        three regions of an arterial wall of the subject at a given        longitudinal location, while    -   (b) allowing the first set of regions of the arterial wall to        pulsate, by    -   implanting a device inside the artery at the longitudinal        location such that the device applies pressure to the arterial        wall at a second set of at least three regions of the artery,        but does not contact the first set of regions, the first set of        regions and the second set of regions alternating with each        other.

For some applications, implanting the device includes increasing strainin the arterial wall at both the first and the second set of regions,relative to the strain in the arterial wall when the device is absentfrom the artery.

For some applications, implanting the device includes increasing across-sectional area of the artery.

For some applications, implanting the device includes implanting adevice such that the second set of regions includes three to six regionsat which the device applies pressure to the arterial wall.

For some applications, implanting the device includes implanting thedevice for less than one month.

For some applications, implanting the device includes implanting thedevice inside a carotid artery of the subject.

For some applications, implanting the device includes implanting thedevice inside a pulmonary artery of the subject.

For some applications, implanting the device includes implanting thedevice inside an aorta of the subject.

For some applications, implanting the device includes placing the deviceinside the artery and allowing the device to become self-anchored to theartery.

For some applications, implanting the device includes implanting adevice having a total cross-sectional area of less than 5 sq mm.

For some applications, implanting the device includes implanting adevice having a total cross-sectional area of less than 0.5 sq mm.

For some applications, increasing the radius of curvature of the firstset of at least three regions of the arterial wall includes increasing asystolic radius of curvature at the regions to more than 1.1 times thesystolic radius of curvature of the arterial wall when the device isabsent from the artery.

For some applications, increasing the radius the curvature of the firstset of at least three regions of the arterial wall includes increasing asystolic radius of curvature at the regions to more than two times thesystolic radius of curvature of the arterial wall when the device isabsent from the artery.

For some applications, increasing the radius the curvature of the firstset of at least three regions of the arterial wall includes increasing asystolic radius of curvature at the regions to more than twenty timesthe systolic radius of curvature of the arterial wall when the device isabsent from the artery.

For some applications, implanting the device includes implanting thedevice such that each of the regions of the first set of regions is acontiguous region that is able to pulsate, each of the contiguousregions encompassing an angle around a longitudinal axis of the arteryof greater than 10 degrees.

For some applications, implanting the device includes implanting thedevice such that each of the regions of the first set of regions is acontiguous region that is able to pulsate, each of the contiguousregions encompassing an angle around the longitudinal axis of the arteryof greater than 20 degrees.

For some applications, implanting the device includes implanting thedevice such that each of the regions of the first set of regions is acontiguous region that is able to pulsate, each of the contiguousregions encompassing an angle around the longitudinal axis of the arteryof greater than 50 degrees.

For some applications, implanting the device includes implanting thedevice such that the first set of regions encompass more than 20 percentof a circumference of the arterial wall at the longitudinal location,during systole of the subject.

For some applications, implanting the device includes implanting thedevice such that the first set of regions encompass more than 80 percentof the circumference of the arterial wall at the longitudinal location,during systole of the subject.

There is further provided, in accordance with some applications of thepresent invention, apparatus for treating hypertension of a subject,including:

an implantable device shaped to define at least three separateartery-contacting surfaces, and configured to:

-   -   (a) increase a radius of curvature of a wall of the artery at a        first set of at least three regions of the arterial wall at a        given longitudinal location, while    -   (b) allowing the first set of regions of the arterial wall to        pulsate at the longitudinal location, by    -   the device being implanted inside the artery at the longitudinal        location such that the artery-contacting surfaces contact a        second set of at least three regions of the arterial wall, but        do not contact the first set of regions of the arterial wall,        the first set of regions and the second set of regions        alternating with each other.

For some applications, the device is configured such that as theartery-contacting surfaces apply increasing pressure to the arterialwall, a cross-sectional area of the artery increases.

For some applications, the device is configured to increase strain inthe arterial wall at both the first and the second set of regions,relative to the strain in the arterial wall when the device is absentfrom the artery.

For some applications, the device is configured to increase across-sectional area of the artery.

For some applications, the artery-contacting surfaces includes three tosix artery contacting surfaces.

For some applications, the device is configured to be implanted insidethe artery for less than one month.

For some applications, the device is configured to be implanted inside acarotid artery of the subject.

For some applications, the device is configured to be implanted inside apulmonary artery of the subject.

For some applications, the device is configured to be implanted insidean aorta of the subject.

For some applications, the device is configured to become self-anchoredto the artery.

For some applications, the device has a total cross-sectional area ofless than 5 sq mm.

For some applications, the device has a total cross-sectional area ofless than 0.5 sq mm.

For some applications, edges of at least two adjacent artery-contactingsurfaces define an angle around a longitudinal axis of the device ofgreater than 10 degrees.

For some applications, the edges of the two artery-contacting surfacesdefine an angle around the longitudinal axis of the device of greaterthan 20 degrees.

For some applications, the edges of the two artery-contacting surfacesdefine an angle around the longitudinal axis of the device of greaterthan 50 degrees.

There is additionally provided, in accordance with some applications ofthe present invention, a method, including:

identifying a subject as suffering from hypertension; and

in response to the identifying,

-   -   (a) increasing strain at a first set of regions of an arterial        wall of the subject at a given longitudinal location,    -   (b) while maintaining, at a given stage in a cardiac cycle of        the subject, a cross-section of the artery at the longitudinal        location that is at least 20 percent of the cross-section of the        artery at the longitudinal location, at the given stage of the        cardiac cycle, when the device is absent, by

implanting a device outside the artery at the longitudinal location suchthat the device applies pressure to the arterial wall at the first setof regions of the arterial wall, but does not contact the arterial wallat at least a second set of regions of the arterial wall at thelongitudinal location, the first set of regions and the second set ofregions alternating with each other.

For some applications, implanting the device includes implanting thedevice outside a carotid artery of the subject.

For some applications, implanting the device includes implanting thedevice outside a pulmonary artery of the subject.

For some applications, implanting the device includes implanting thedevice outside an aorta of the subject.

For some applications, maintaining the cross-section of the artery thatis at least 20 percent of the cross-section of the artery at thelongitudinal location when the device is absent, includes maintaining aninternal diameter of the artery, in the presence of the device, that isat least 30 percent of the diameter of the artery in the absence of thedevice.

For some applications, maintaining the cross-section of the artery thatis at least 20 percent of the cross-section of the artery at thelongitudinal location when the device is absent, includes maintaining arate of blood flow through the artery that is more than 70 percent ofthe rate of blood flow through the artery in the absence of the device.

For some applications, maintaining the rate of blood flow through theartery that is more than 70 percent of the rate of blood flow throughthe artery in the absence of the device, includes maintaining a rate ofblood flow through the artery that is more than 90 percent of the rateof blood flow through the artery in the absence of the device.

For some applications, implanting the device includes implanting thedevice such that the arterial wall is able to pulsate at each of thesecond set of regions.

For some applications, implanting the device includes implanting adevice outside the artery at the longitudinal location such that thedevice applies pressure to the arterial wall at a first set of three tosix regions of the artery, but does not contact the artery at a secondset of three to six regions of the artery.

For some applications, implanting the device includes implanting adevice outside the artery at the longitudinal location such that thedevice does not contact the artery at at least the second set of regionsof the artery, each of the second set of regions being contiguous, andencompassing an angle around a longitudinal axis of the artery ofgreater than 10 degrees.

For some applications, implanting the device includes implanting adevice such that each of the second set of regions encompasses an anglearound the longitudinal axis of the artery of greater than 20 degrees.

For some applications, implanting the device includes implanting adevice such that each of the second set of regions encompasses an anglearound the longitudinal axis of the artery of greater than 50 degrees.

For some applications, implanting the device includes implanting thedevice such that the device encompasses less than 90 percent of acircumference of the artery.

For some applications, implanting the device includes implanting thedevice such that the device encompasses less than 70 percent of thecircumference of the artery.

There is additionally provided, in accordance with some applications ofthe present invention, apparatus for treating hypertension of a subject,including:

an implantable device shaped to define a single pair ofartery-contacting surfaces, and configured to:

-   -   (a) increase a radius of curvature of the artery at a first set        of two regions of the artery at a given longitudinal location,        while    -   (b) allowing the first set of regions of the artery to pulsate        at the longitudinal location, by    -   the device being implanted inside the artery at the longitudinal        location such that the artery-contacting surfaces contact a        second set of two regions of the artery, but at no point during        a cardiac cycle of the subject does the device contact the first        set of regions, the first set of regions and the second set of        regions alternating with each other.

For some applications, the device is configured such that when thedevice is implanted in the artery no portion of the device intersects alongitudinal axis of the artery.

For some applications, the device further includes a joint configured tocouple the artery-contacting surfaces to one another, and the joint isdisposed asymmetrically with respect to centers of the artery-contactingsurfaces.

There is further provided, in accordance with some applications of thepresent invention, apparatus configured to be implanted into an arteryof a subject via a catheter, the apparatus including:

an implantable device shaped to define:

-   -   at least two artery-contact regions, the artery-contact regions        including struts that are configured to stretch an arterial wall        by applying pressure to the arterial wall, and    -   at least two crimping regions that include locking mechanisms        configured to prevent the crimping regions from becoming crimped        due to pressure from the wall of the artery on the        artery-contact regions,    -   the crimping regions being configured to be crimped during        insertion of the device, via the catheter, by the locking        mechanisms being unlocked during insertion of the device via the        catheter.

For some applications, the crimping region defines two struts that aredisposed adjacently to one another, and the locking mechanism includesan interface between the two struts that locks the struts with respectto one another.

For some applications, an end of at least one of the artery-contactregions defines a crimping arch, the artery-contact region beingconfigured to be crimped about the crimping arch, the crimping archhaving a radius of curvature of less than 0.6 mm.

For some applications, the end of the artery contact-region defines acrimping arch having a radius of curvature of more than 0.3 mm.

For some applications, the struts of the artery-contact regions projectoutwardly from the crimping arch at an angle that is greater than 30degrees.

For some applications, the struts of the artery-contact regions projectoutwardly from the crimping arch at an angle that is greater than 60degrees.

For some applications, the struts of the artery-contact regions projectoutwardly from the crimping arch at an angle that is greater than 75degrees.

For some applications, a maximum span of the device increases along adirection of a longitudinal axis of the device from a first end of thedevice to a second end of the device.

For some applications, the second end of the device is configured to beplaced in a carotid sinus of the subject, and the first end of thedevice is configured to be placed in an internal carotid artery of thesubject.

For some applications, a ratio of the maximum span of the device at thesecond end of the device to the maximum span of the device at the firstend of the device is between 1.1:1 and 2:1.

For some applications, a ratio of the maximum span of the device at thesecond end of the device to the maximum span of the device at the firstend of the device is between 1.1:1 and 1.4:1.

For some applications, the artery-contacting regions each include two ormore struts that are longitudinally translated with respect to oneanother.

For some applications, the apparatus further includes a reinforcingelement configured to couple the two or more struts to one another, andto maintain the longitudinal translation of the struts with respect toone another when the device is crimped.

For some applications, the device has a total cross-sectional area ofless than 5 sq mm.

For some applications, the device has a total cross-sectional area ofless than 0.5 sq mm.

There is additionally provided, in accordance with some applications ofthe present invention, apparatus, including:

an implantable device shaped to define at least two separateartery-contacting strut portions that diverge from each other, from afirst end of the device to a second end of the device, and configured:

-   -   to cause a cross-sectional area of a portion of the artery to        increase from the first end of the portion to the second end of        the portion, while allowing a set of regions of the arterial        wall of the portion that are between the struts to pulsate,    -   by the device being implanted inside the artery between the        first and second ends of the portion.

For some applications, at least one end of the device defines a crimpingarch, the device being configured to be crimped about the crimping arch,the crimping arch having a radius of curvature of less than 0.6 mm.

For some applications, the end of the device defines a crimping archhaving a radius of curvature of more than 0.3 mm.

For some applications, struts of the strut portions project outwardlyfrom the crimping arch at an angle that is greater than 30 degrees.

For some applications, the struts of the strut portions projectoutwardly from the crimping arch at an angle that is greater than 60degrees.

For some applications, the struts of the strut portions projectoutwardly from the crimping arch at an angle that is greater than 75degrees.

For some applications, a maximum span of the device increases along adirection of a longitudinal axis of the device from a first end of thedevice to a second end of the device.

For some applications, the second end of the device is configured to beplaced in a carotid sinus of the subject, and the first end of thedevice is configured to be placed in an internal carotid artery of thesubject.

For some applications, a ratio of the maximum span of the device at thesecond end of the device to the maximum span of the device at the firstend of the device is between 1.1:1 and 2:1.

For some applications, a ratio of the maximum span of the device at thesecond end of the device to the maximum span of the device at the firstend of the device is between 1.1:1 and 1.4:1.

For some applications, the strut portions each include two or morestruts that are longitudinally translated with respect to one another.

For some applications, the apparatus further includes a reinforcingelement configured to couple the two or more struts to one another, andto maintain the longitudinal translation of the struts with respect toone another when the device is crimped.

For some applications, the device has a total cross-sectional area ofless than 5 sq mm.

For some applications, the device has a total cross-sectional area ofless than 0.5 sq mm.

There is further provided, in accordance with some applications of thepresent invention, apparatus, including:

an implantable device shaped to define at least four artery-contactingstrut portions that are parallel to each other,

each of the strut portions being disposed at a first distance from afirst adjacent strut portion, and at a second distance from a secondadjacent strut portion, the second distance being greater than the firstdistance.

For some applications, the at least four artery-contacting strutportions include exactly four artery-contacting strut portions.

For some applications, a ratio of the second distance to the firstdistance is between 1.1:1 and 5:1.

For some applications, the ratio of the second distance to the firstdistance is between 1.5:1 and 3:1.

For some applications, the device has a total cross-sectional area ofless than 5 sq mm.

For some applications, the device has a total cross-sectional area ofless than 0.5 sq mm.

For some applications, at least one end of the device defines a crimpingarch, the device being configured to be crimped about the crimping arch,the crimping arch having a radius of curvature of less than 0.6 mm.

For some applications, the end of the device defines a crimping archhaving a radius of curvature of more than 0.3 mm.

For some applications, struts of the strut portions project outwardlyfrom the crimping arch at an angle that is greater than 30 degrees.

For some applications, the struts of the strut portions projectoutwardly from the crimping arch at an angle that is greater than 60degrees.

For some applications, the struts of the strut portions projectoutwardly from the crimping arch at an angle that is greater than 75degrees.

There is further provided, in accordance with some applications of thepresent invention, a method, including:

inserting into an artery of a subject, via a catheter, an implantabledevice that is shaped to define:

-   -   at least two artery-contact regions, the artery-contact regions        including struts, and    -   at least two crimping regions that include locking mechanisms        configured to prevent the crimping regions from becoming crimped        due to pressure from the wall of the artery on the        artery-contact regions,    -   the insertion being performed by crimping the crimping regions        during insertion of the device, by unlocking the locking        mechanism during insertion of the device via the catheter;

advancing the device out of a distal end of the catheter; and

upon advancing the device out of the distal end of the catheter,stretching a wall of the artery by applying pressure to the arterialwall with the struts, by locking the locking mechanism.

There is additionally provided, in accordance with some applications ofthe present invention, a method, including:

identifying a subject as suffering from hypertension; and

in response thereto:

-   -   causing a cross-sectional area of a portion of an artery of the        subject to increase from the first end of the portion to the        second end of the portion, while allowing a set of regions of        the arterial wall of the portion to pulsate,    -   by implanting inside the artery, between the first and second        ends of the portion, an implantable device shaped to define at        least two separate artery-contacting strut portions that diverge        from each other, from a first end of the device to a second end        of the device.

There is additionally provided, in accordance with some applications ofthe present invention, a method for treating hypertension in a patient,said method including:

selecting a patient diagnosed with hypertension; and

implanting a device proximate a baroreceptor in a blood vessel wall ofthe patient proximate the baroreceptor, the blood vessel having agenerally cylindrical circumference prior to implanting the device, theimplanting of the device flattening one or more regions about thecircumference to reduce systemic blood pressure.

For some applications, the device is implanted in an artery selectedfrom the group consisting of a renal artery, the aorta, a subclavianartery, a carotid artery, and an artery of the brain.

For some applications, 3 to 6 regions are flattened.

For some applications, 3 to 4 regions are flattened.

For some applications, 3 regions are flattened.

For some applications, 4 regions are flattened.

For some applications, the flattened regions have substantially equalwidths in the circumferential direction.

For some applications, at least some of the flattened regions havedifferent widths in the circumferential direction than do others of thecircumferential portions.

For some applications, the device flattens regions that extend along alength of the blood vessel wall in the range from 10 mm to 30 mm.

There is additionally provided, in accordance with some applications ofthe present invention, a self-expanding stent consisting of from threeto six elongate struts, each strut having a proximal end and a distalend, said struts being expandably coupled to each other at theirproximal and distal ends but otherwise being free from structuretherebetween along their lengths.

For some applications, the struts are arranged axially.

For some applications, the struts are arranged helically.

For some applications, adjacent struts are equally spaced-apart fromeach other.

For some applications, not all adjacent struts are equally spaced-apart.

For some applications, the struts have a length of at least 10 mmbetween their proximal and distal ends.

The present invention will be more fully understood from the followingdetailed description of embodiments thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional illustration of an artery;

FIGS. 2A-B are contour plots of the strain in the wall of an artery,respectively, when the artery does have and does not have insertedtherein an intravascular device, in accordance with some applications ofthe present invention;

FIG. 3 is a contour plot of the strain in the wall of an artery, anextravascular device having been implanted outside the wall, inaccordance with some applications of the present invention;

FIG. 4 is a schematic illustration of an intravascular device forplacing inside an artery of a subject suffering from hypertension, inaccordance with some applications of the present invention;

FIGS. 5A-B are schematic illustrations of an artery, showing the radiusof curvature of the artery, respectively, before and after placement ofthe device shown in FIG. 4, in accordance with some applications of thepresent invention;

FIG. 5C is a schematic illustration of the device of FIG. 4 disposedinside the artery, without stretching the artery, for illustrativepurposes;

FIGS. 6A-B are schematic illustrations of, respectively, a device, andthe device implanted inside an artery, in accordance with someapplications of the present invention;

FIGS. 7A-B are schematic illustrations of, respectively, another device,and the device implanted inside an artery, in accordance with someapplications of the present invention;

FIGS. 8A-B are schematic illustrations of, respectively, a furtherdevice, and the device implanted inside an artery, in accordance withsome applications of the present invention;

FIGS. 9A-D are schematic illustrations of extravascular devices placedaround an artery, in accordance with some applications of the presentinvention;

FIG. 10 is a graph that indicates the portion of an arterial wall havinga strain that is greater than a threshold value, as a function of thereduction in the cross-sectional area of the artery, for respectiveextravascular devices, in accordance with some applications of thepresent invention;

FIG. 11 is a graph showing the maximum percentage increase in the strainof the arterial wall as a function of the reduction in thecross-sectional area of the artery, for respective extravasculardevices, in accordance with some applications of the present invention;

FIG. 12 is a schematic illustration of a device for measuring thebaroreceptor response of a subject to pressure that is exerted on theinner wall of an artery of the subject, in accordance with someapplications of the present invention;

FIG. 13 is a graph showing the blood pressure measured in a dog beforeand after the insertion of intravascular devices into the dog's carotidsinuses, in accordance with some applications of the present invention;

FIG. 14 is a graph showing the pressure-strain curve of the artery of ahealthy subject, a hypertensive subject, and a hypertensive subject thatuses a device as described herein, in accordance with some applicationsof the present invention;

FIGS. 15A-B are schematic illustrations of a device for placing in asubject's artery, in accordance with some applications of the presentinvention;

FIGS. 15C-D are schematic illustrations of an arterial wall exerting aforce on struts of a device, in accordance with some applications of thepresent invention;

FIGS. 16A-D are schematic illustrations of another device for placing ina subject's artery, in accordance with some applications of the presentinvention;

FIGS. 17A-D are schematic illustrations of yet another device forplacing in a subject's artery, in accordance with some applications ofthe present invention;

FIGS. 18A-D are schematic illustrations of further devices for placingin a subject's artery, in accordance with some applications of thepresent invention;

FIG. 19 is a schematic illustration of a device having a D-shapedcross-section for placing in a subject's artery, in accordance with someapplications of the present invention; and

FIG. 20 is a graph showing the derivative of strain versus pressure as afunction of rotational position around the artery, in accordance withrespective models of an artery, in accordance with some applications ofthe present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is now made to FIG. 1, which is a cross-sectional illustrationof an artery 20. The arterial wall includes three layers 22, 24, and 26,which are called, respectively, the intima, the media, and theadventitia. For some applications of the present invention, anintravascular device is placed inside an artery, baroreceptors beingdisposed at the interface between adventitia 26 and media 24 of theartery. The device causes the curvature of the arterial wall to flattenin some regions of the circumference of the arterial wall, therebycausing the baroreceptors to become stretched, while allowing theregions to pulsate over the course of the subject's cardiac cycle.

Reference is now made to FIGS. 2A and 2B, which are contour plots of thestrain in the top right quarter of an arterial wall, in the absence ofan intravascular device (FIG. 2A) and in the presence of anintravascular device (FIG. 2B), analyzed and/or provided in accordancewith some applications of the present invention. The contour plot inFIG. 2B was generated for a device (e.g., as shown hereinbelow in FIGS.7A-B) having four elements, each of which contacts the arterial wall ata contact region 42. The contour plots shown in FIGS. 2A-B are computersimulations of the strain in the wall of an artery, at a blood pressureof 100 mmHg, the artery having a radius of 3 mm, and a wall thickness of0.6 mm. The scope of the present application includes intravasculardevices having different structures from that used to generate FIG. 2B,as would be obvious to one skilled in the art.

As seen in FIGS. 2A-B, relative to the strain in the arterial wall inthe absence of an intravascular device, the intravascular device causesthere to be increased strain in the arterial wall both (a) in thevicinity of contact regions 42, at which the arterial wall becomes morecurved than in the absence of the device, and (b) in flattened regions44 of the wall, in which regions the arterial wall is flatter than it isin the absence of the device. Thus, the intravascular device increasesthe strain in the arterial wall even in regions of the arterial wallwhich are able to pulsate, i.e., flattened regions 44. The increasedstrain in the flattened regions relative to the strain in the wall inthe absence of the intravascular device is due to the increased radiusof curvature of the flattened regions of the wall.

Reference is now made to FIG. 3, which is a contour plot of the strainin the top right quarter of an arterial wall, in the presence of anextravascular device, in accordance with some applications of thepresent invention. The contour plot in FIG. 3 was generated for a devicehaving four elements that contact the artery at four contact regions 52.However, the scope of the present invention includes extravasculardevices having different structures, as described hereinbelow. Forexample, an extravascular device may provide three to six contactregions. The contour plot shown in FIG. 3 is a computer simulation ofthe strain in the wall of an artery, at a blood pressure of 100 mmHg,the artery having a radius of 3 mm, and a wall thickness of 0.6 mm.

As may be observed by comparing FIG. 3 to FIG. 2A, the extravasculardevice causes there to be strain in the arterial wall in the vicinity ofcontact regions 52, at which the arterial wall becomes more curved thanin the absence of the device. Furthermore, it may be observed that thestrain at non-contact regions 54 of the wall is lower than in theabsence of the device. The extravascular device typically breaks thecircumferential symmetry of the arterial strain by applying force atdiscrete points or surfaces around the sinus. For some applications, theextravascular device increases the strain in certain regions of thearterial wall, and decreases the strain in other regions of the arterialwall, while maintaining the average strain almost unchanged or evenslightly reduced with respect to the strain in the wall in the absenceof the device. For some applications, the extravascular device increasesthe strain in the arterial wall even at non-contact regions 54, bycausing the non-contact regions to become more curved than in theabsence of the device.

Reference is now made to FIG. 4, which is a schematic illustration of anintravascular device 60 for placing inside artery 20 of a subjectsuffering from hypertension, in accordance with some applications of thepresent invention. As shown, device 60 contacts the arterial wall at twocontact regions 62. At the contact regions, device 60 pushes thearterial wall outward, thereby flattening non-contact regions 64 of thearterial wall between the contact regions. Typically, non-contactregions 64 are flattened, or partially flattened during diastole of thesubject, but expand during systole such that they become more curvedthan during diastole. Therefore, strain in the flattened regions of thearterial wall is increased. However, the flattened regions still pulsateover the course of the subject's cardiac cycle in the presence of device60.

As shown, device 60 is shaped such that the device substantially doesnot reduce blood flow. Typically, device 60 is shaped such that noportion of the device intersects the longitudinal axis of the artery.For example, as shown, contact surfaces of the device (which contact thearterial wall at contact regions 60) are coupled to each other by ajoint 66 that does not intersect the longitudinal axis of the artery.The joint is disposed asymmetrically with respect to centers of thecontact surfaces of the device.

Reference is now made to FIGS. 5A-B, which are schematic illustrationsof an artery, showing the radius R of artery 20, respectively, beforeand after placement of the device 60 shown in FIG. 4, in accordance withsome applications of the present invention. It may be observed that, forsome applications, insertion of device 60 increases the systolic radiusof curvature of the artery at non-contact regions 64, for example, suchthat the radius of curvature at non-contact regions 64 is more than 1.1times (e.g., twice, or more than twenty times) the systolic radius ofcurvature of regions 64 in the absence of device 60, ceteris paribus.For some applications, device 60 causes the radius of curvature of atleast a portion of a non-contact region to become infinite, byflattening the non-contact regions. For example, the center ofnon-contact region 64 in FIG. 5B has an infinite radius of curvature.

For some applications, device 60 increases the systolic radius ofcurvature of the artery at non-contact regions 64 in the aforementionedmanner, and increases the systolic cross-sectional area of the artery bymore than five percent (e.g., ten percent), relative to the systoliccross-sectional area of the artery in the absence of device 60.

In accordance with the description hereinabove, by flatteningnon-contact regions 64 of the wall of artery 20, device 60 causesincreased strain in regions 64, thereby causing an increase inbaroreceptor firing at regions 64. Alternatively or additionally, device60 causes increased baroreceptor firing at contact regions 62, bydeforming the arterial wall at the contact regions.

Typically, device 60 exerts a force on artery 20, such that, duringsystole when the artery is in the stretched configuration shown in FIG.5B, non-contact regions 64 comprise more than ten percent, e.g., morethan 20 percent, of the circumference of the arterial wall atlongitudinal sites at which device 60 stretches the artery. For someapplications, during systole, non-contact regions 64 comprise more than60 percent, e.g., more than 80 percent, of the circumference of thearterial wall at longitudinal sites at which device 60 stretches theartery.

Reference is now made to FIG. 5C, which shows device 60 disposed insideartery 20, but without the device stretching artery 20. FIG. 5C is forillustrative purposes, since typically once device 60 is inserted intothe artery, the device will stretch the artery, as shown in FIG. 5B.FIG. 5C demonstrates that the device contacts the walls of the artery atcontact regions 62 at less than 360 degrees of the circumference of theartery at any longitudinal point along artery 20 (e.g., at thecross-section shown in FIGS. 5A-C). As shown in FIG. 5C, each of thecontact regions 62 encompasses an angle alpha of the circumference ofthe artery, such that the contact that device 60 makes with the walls ofthe artery encompasses two times alpha degrees. For devices that contactthe artery at more than two contact regions, the contact that the devicemakes with the walls of the artery encompasses an angle that is acorrespondingly greater multiple of alpha degrees. Typically, device 60(and the other intravascular devices described herein) contacts thewalls of the artery at less than 180 degrees (e.g., less than 90degrees) of the circumference of the artery at any longitudinal sitealong the artery. Typically, device 60 contacts the walls of the arteryat more than 5 degrees (e.g., more than 10 degrees) of the circumferenceof the artery at any longitudinal site along the artery. For example,device 60 may contact the walls of the artery at 5-180 degrees, e.g.,10-90 degrees, at a given longitudinal site.

Reference is now made to FIGS. 6A-B, which are schematic illustrationsof, respectively, a device 70, and device 70 implanted inside artery 20,in accordance with some applications of the present invention. Device 70contacts the wall of the artery at three contact regions 72, therebyincreasing the radius of curvature (i.e., flattening) of non-contactregions 74 of the artery that are between the contact regions. Theflattened non-contact regions and the contact regions alternate witheach other. The flattened non-contact regions are typically able topulsate over the course of the subject's cardiac cycle, as describedhereinabove. As shown in FIG. 6B, each contiguous non-contact region ata given longitudinal site of the artery, encompasses an angle betaaround a longitudinal axis 76 of the artery. For some devices (e.g.,device 70, and device 90 described hereinbelow with reference to FIGS.8A-B), the angle beta is also defined by the angle that edges ofadjacent contact regions of the device define around longitudinal axis78 of the device. When the device is placed in the artery longitudinalaxis 78 of the device is typically aligned with longitudinal axis 76 ofthe artery. Typically, angle beta is greater than 10 degree, e.g.,greater than 20 degree, or greater than 50 degrees. Further typically,angle beta is less than 180 degrees, e.g., less than 90 degrees. Forsome applications angle beta is 10-180 degree, e.g., 20-90 degrees.Typically, each of the contiguous non-contact regions is able topulsate.

Reference is now made to FIGS. 7A-B, which are schematic illustrationsof, respectively, a device 80, and device 80 implanted inside artery 20,in accordance with some applications of the present invention. Device 80contacts the wall of the artery at four contact regions, therebyflattening the non-contact regions of the artery that are between thecontact regions. Each contiguous non-contact region at a givenlongitudinal site of the artery, encompasses an angle beta around thelongitudinal axis of the artery, angle beta being as describedhereinabove.

Reference is now made to FIGS. 8A-B, which are schematic illustrationsof, respectively, a device 90, and device 90 implanted inside artery 20,in accordance with some applications of the present invention. Device 90contacts the wall of the artery at five contact regions, therebyflattening the non-contact regions of the artery that are between thecontact regions. Each contiguous non-contact region at a givenlongitudinal site of the artery, encompasses an angle beta around thelongitudinal axis of, angle beta being as described hereinabove.

Apart from the fact that devices 70, 80, and 90 contact the artery at,respectively three, four, and five contact regions, devices 70, 80, and90 function in a generally similar manner to each other, and to device60, described with reference to FIGS. 4 and 5A-C. For example, devices70, 80, and 90 typically contact the arterial wall around substantiallyless than 360 degrees of the circumference of the artery, for example,around 10-90 degrees, or around an angle as described hereinabove withreference to FIGS. 5A-C. Furthermore, devices 70, 80, and typicallyincrease the cross-sectional area of the artery relative to thecross-sectional area of the artery in the absence of the device.

For some applications, a device having three or more contact regionswith the arterial wall, for example, as shown in FIGS. 6A-8B, is used.It is noted that since device 60 (shown in FIG. 4) contacts the arteryat two contact points, as the device applies increasing pressure to theartery, it will, at a given stage, decrease the cross-section of theartery, as the artery becomes increasingly elliptical. By contrast,devices 70, 80, and 90, which contact the artery at three or morecontact points, increase the cross-section of the artery, as they applyincreasing pressure to the wall of the artery. Thus, for someapplications, a device with three or more contact regions is used inorder that the cross-sectional area of the artery is increased as theforce which the device exerts on the wall increases, as compared with adevice with only two contact regions.

Although devices that contact artery 20 at two, three, four and fivecontact regions have been described, the scope of the present inventionincludes devices that contact the artery at a different number ofcontact regions, and/or that have different structures from those shown,mutatis mutandis.

The intravascular devices described herein are generally shaped suchthat the devices contact the intravascular wall at relatively smallcontact regions, and provide relatively large contiguous non-contactregions, which are able to pulsate due to the subject's cardiac cycle.

The devices are typically shaped such that the total contact region thatthe device makes with the arterial wall at any longitudinal point alongthe artery is less than 2 mm, e.g., less than 0.5 mm. The contact regionis usually larger than 0.05 mm, e.g., greater than 0.2 mm. For example,the contact region may be 0.05-2 mm, e.g., 0.1-0.4 mm, or 0.2-0.5 mm.The devices are typically inserted into an artery that has an internalcircumference during systole of 6-8 mm. Thus, the intravascular devicesdescribed herein are typically configured to contact less than 35percent of the circumference of the artery at any longitudinal pointalong the artery, and at any point in the subject's cardiac cycle (or,for at least a portion of the cardiac cycle). Further typically, theintravascular devices described herein are configured to contact morethan 0.5 percent of the circumference of the artery at any longitudinalpoint along the artery, and at any point in the subject's cardiac cycle(or, for at least a portion of the cardiac cycle). For someapplications, the contact region may be 0.5-35 percent of thecircumference of the artery (or, for at least a portion of the cardiaccycle).

For some applications, the intravascular devices described herein have atotal cross-sectional area of less than 5 sq mm, e.g., less than 0.8 sqmm, or less than 0.5 sq mm. (The total cross-sectional area should beunderstood to refer to the cross-sectional area of the solid portions ofthe devices, and not the space in between the solid portions.) Thedevices typically have this cross-sectional area over a length of thedevice of more than 4 mm, e.g., more than 6 mm, and/or less than 12 mm,e.g. less than 10 mm. For example, the devices may have theaforementioned cross sectional area over a length of 4 mm-12 mm, e.g., 6mm-10 mm. The devices are typically manufactured from nitinol, and/orpassivated stainless steel 316L.

Reference is now made to FIGS. 9A-D, which are schematic illustrationsof extravascular devices 100 that are implanted around the outside ofartery 20, in accordance with some applications of the presentinvention. For some applications, an extravascular device having threecontact elements 102 (as shown in FIGS. 9A and 9C) is placed around theartery. Alternatively, the extravascular device has a different numberof contact elements 102, e.g., four to six contact elements. The contactelements increase the strain in the arterial wall at the regions atwhich the contact elements contact the arterial wall, relative to thestrain in the arterial wall in the absence of device 100. For someapplications, the device increases the strain in the arterial wall evenat regions of the arterial wall between the contact regions, relative tothe strain of the arterial wall in the absence of the device.

As with the intravascular devices described hereinabove, typicallycontact between extravascular device 100 and the artery at a givenlongitudinal location is limited to several (e.g., three to six) contactregions around the circumference of the artery, and is generallyminimized. Thus, when the device is placed around the artery there is atleast one, and typically a plurality of, non-contact regions 104 aroundthe circumference of the artery, at which the device does not contactthe arterial wall. As shown in FIG. 9A, each contiguous non-contactregion at a given longitudinal site of the artery, encompasses an angletheta around a longitudinal axis 76 of the artery. For some devices, asshown, the angle theta is also defined by the edges of adjacent contactelements 102 of the device and longitudinal axis 108 of the device. Whenthe device is placed in the artery longitudinal axis 108 of the deviceis typically aligned with longitudinal axis 76 of the artery.

Typically, angle theta is greater than 10 degree, e.g., greater than 20degree, or greater than 50 degrees. Further typically, angle theta isless than 180 degrees, e.g., less than 90 degrees. For some applicationsangle theta is 10-180 degree, e.g., 20-90 degrees. This may bebeneficial, since providing contiguous non-contact regions around theartery, as described, allows a greater area of the artery to pulsate inresponse to pressure changes than if the device were to provide smallercontiguous non-contact regions.

FIG. 9E shows a cross-section of one of contact elements 102 on a wallof artery 20, in accordance with some applications of the presentinvention. For some applications, some or all of contact elements 102are shaped to define grooves. Each of the grooves has a length L.Typically, length L is more than 0.5 mm (e.g., more than 2 mm), and/orless than 8 mm (e.g., less than 6 mm). For example, length L may be0.5-8 mm, e.g., 2-6 mm. The contact element typically facilitatespulsation of the arterial wall into the groove.

Typically (as shown for example in FIGS. 9A and 9C), extravasculardevice 100 does not encompass the full circumference of the artery. Forexample, the extravascular device may encompass less than 90 percent,e.g., less than 70 percent of the circumference of the artery. For someapplications, using a device that does not encompass the wholecircumference of the artery facilitates placement of the device on theartery. For example, it may be possible to place such a device on theartery (a) without dissecting the artery free from its surroundingtissues, and/or (b) without fully mobilizing the artery.

For some applications, using a device that does not encompass the wholecircumference of the artery reduces damage to the artery, and/or damageto baroreceptors, during placement of the device on the artery.Alternatively or additionally, using a device that does not encompassthe whole circumference of the artery makes placement of the device onthe artery a less complex procedure than placement on the artery of adevice that fully encompasses the artery.

For some applications, device 100 does not encompass the wholecircumference of the artery, and contact elements 102 curve around theartery, as shown in FIG. 9C. Typically, the curvature of the contactelements facilitates coupling of device 100 to the artery.

Typically, extravascular device 100 encompasses more than 50 percent ofthe circumference of the artery, for example, in order to prevent thedevice from slipping from the artery. However, the scope of the presentinvention includes devices that encompass less than 50 percent of theartery.

For some applications, extravascular device 100 encompasses the wholecircumference of artery 20. For example, an extravascular device may beused that comprises two pieces that are coupled to each other such thatthe device encompasses the whole artery.

Typically, the device causes an increase in the strain in at least aportion of the arterial wall, relative to the strain in the arterialwall in the absence of the device, without substantially reducing thecross-sectional area of the artery. For example, the cross-sectionalarea of the artery in the presence of device 100 may be more than 50percent, e.g., more than 80 percent of the cross-sectional area of theartery in the absence of the device, at a given stage in the subject'scardiac cycle. The device does not cause a substantial reduction in thecross-sectional area of the artery because the device only contacts theartery at discrete points around the circumference of the artery.Therefore the device does not substantially constrict the artery, butrather reshapes the artery relative to the shape of the artery in theabsence of the device.

Further typically, the device causes an increase in the strain in atleast a portion of the arterial wall, relative to the strain in thearterial wall in the absence of the device, without substantiallyaffecting blood flow through the artery. For example, the rate of bloodflow through the artery in the presence of device 100 may be more than70 percent, e.g., more than 90 percent of the blood flow in the absenceof the device.

For some applications, an insubstantial effect on flow is achieved bymaintaining an internal diameter of the artery, in the presence of thedevice, that is at least 30 percent of the diameter of the artery, inthe absence of the device, throughout the cardiac cycle. Alternativelyor additionally, an insubstantial effect on flow is achieved bymaintaining the cross sectional area of the artery, in the presence ofthe device, to be at least 20 percent of the sectional area, in theabsence of the device, at a given stage in the subject's cardiac cycle.

For some applications, the flow through the artery to which the deviceis coupled is monitored during the implantation of the device, and thedevice is configured to not reduce the flow by more than 15 percent. Forsome applications, the degree of force applied to the artery, and/or aphysical distance between parts of the device, is modulated until themeasured flow is not reduced by more than 15 percent. For someapplications the absolute minimal distance across the artery is limitedto no less than 1.5 mm.

For some applications, the extravascular devices contact the arteryaround which they are placed along a length of 5 mm.

For some applications, an extravascular device is used that is inaccordance with one or more of the devices described in U.S. patentapplication Ser. No. 12/602,787 to Gross, which is incorporated hereinby reference.

For some applications, a plurality of extravascular devices 100 areplaced around the artery, as shown in FIG. 9D. For some applications,the plurality of extravascular devices are coupled to each other by acoupling element 105. The extravascular devices are typically spacedfrom each other such that there are non-contact regions 103 between eachof the extravascular devices. Each of the non-contact regions iscontiguous and, typically, has a length L1 of more than 0.5 mm (e.g.,more than 2 mm), and/or less than 8 mm (e.g., less than 6 mm). Forexample, length L1 may be 0.5-8 mm, e.g., 2-6 mm. The arterial wall istypically able to pulsate at the non-contact regions.

Reference is now made to FIG. 10, which is a graph generated by computersimulation, which indicates the circumferential portion of an arterialwall having a strain that is greater than a threshold value, as afunction of the reduction in the cross-sectional area of the artery, forrespective extravascular devices. For some applications of the presentinvention, an extravascular device is placed around an artery, asdescribed hereinabove. Typically, the extravascular device increasesstrain in at least regions of the arterial wall without substantiallyreducing the cross-sectional area of the artery, as describedhereinabove. Further typically, the extravascular device increasesstrain in at least regions of the arterial wall without substantiallyaffecting blood flow through the artery, as described hereinabove.

The graph shows several lines, the lines corresponding to extravasculardevices that are similar to the extravascular device describedhereinabove with reference to FIGS. 3 and 9A. The lines correspond toextravascular devices that have, respectively, three, four, five, six,and seven contact regions with the arterial wall around thecircumference of the artery. In addition, one of the lines correspondsto two flat plates that are placed against the outer surface of theartery.

The simulation was generated for an artery at 100 mmHg of pressure. Whenthe extravascular devices herein are placed on the arterial wall, thestrain in at least some portions of the arterial wall is increased.Placing the extravascular devices on the arterial wall typically reducesthe cross-sectional area of the artery. For a given device, the more thedevice compresses the artery, the greater the increase in the strain inthe arterial walls, and the greater the reduction in the cross-sectionalarea of the artery.

The x-axis of the graph of FIG. 10 indicates the reduction in thecross-sectional area of the artery generated by the devices. The y-axismeasures the percentage of the circumference of the arterial wall havinga strain that is at least equivalent to what the strain of the arterialwall would be, if the pressure in the artery were 120 mmHg. Typically,the baroreceptor firing rate in such areas when the pressure is 100mmHg, during use of the devices described hereinabove, will be generallyequivalent to, or greater than the baroreceptor firing rate at 120 mmHgpressure in the absence of use of the devices. Thus, each of the linesin the graph is a measure of the percentage of the circumference of thearterial wall having the increased strain as a function of the reductionin the arterial cross-sectional area that is necessary to induce theincrease in strain.

It may be observed that the devices having a smaller number of contactregions with the artery are typically more effective at increasing thestrain in the arterial wall by applying a compression force that doesnot substantially reduce the cross-sectional area of the artery. Forexample, devices having three and four contact regions with the arteryincrease the strain of, respectively, 13 percent and 14 percent of thearterial wall to the equivalent of 120 mmHg of pressure while onlyreducing the cross-sectional area of the artery by 10 percent.Typically, a 10 percent reduction in the cross-sectional area of theartery does not substantially reduce blood flow through the artery in amanner that has significant adverse physiological effects.

The inventors hypothesize that the devices having a larger number ofcontact regions with the artery are less effective at increasing thestrain in the arterial wall than those with a smaller number of contactregions, because the device acts to support the arterial wall at thecontact regions, thereby reducing pulsation of the arterial wall overthe course of the cardiac cycle. For this reason, the inventorshypothesize that, at low pressures, the two plates are relativelyeffective at increasing the strain in the arterial wall, since there isa small amount of contact between the plates and the wall. However, athigher compressive forces, the plates provide more support to the wallsince there is a greater contact area between the plates and the wall.Therefore, the plates limit the pulsation of the wall by an increasingamount. At higher compressive forces, the decrease in baroreceptorstimulation due to the reduced pulsation of the artery overrides theincrease in baroreceptor stimulation due to the plates exerting pressureon the arterial wall. Thus, at higher compressive forces, the plates arenot as effective as the other extravascular devices at increasing thestrain in regions of the arterial wall. Nevertheless, the scope of thepresent invention include the use of such plates, e.g., when strainincrease is not the only parameter of importance in selecting animplant.

It is additionally noted that for a broad range of allowed reductions incross-section, e.g., about 17-30 percent, 3-6 contact regions allfunction generally well. Thus, at higher compression forces (i.e., byreducing the cross-sectional area of the artery by a greater amount),the devices having a greater number of contact regions with the arterybecome more effective at increasing the strain in the arterial wall. Forexample, by reducing the cross-sectional area of the artery by 30percent, each of the devices having three to six contact regions withthe artery increases the strain of between 22 percent and 26 percent ofthe arterial wall to the equivalent of 120 mmHg of pressure.

Reference is now made to FIG. 11, which is a graph showing the maximumpercentage increase in the strain of the arterial wall as a function ofthe reduction in the cross-sectional area of the artery, for respectiveextravascular devices.

The graph shows several lines, the lines corresponding to extravasculardevices that are similar to the extravascular device describedhereinabove with reference to FIGS. 3 and 9A. The lines correspond toextravascular devices that have, respectively, three, four, five, six,and seven contact regions with the arterial wall around thecircumference of the artery. In addition, one of the lines correspondsto two plates that are placed against the outside surface of the artery.

The simulation was generated for an artery at 100 mmHg of pressure. Thebottom, middle, and top horizontal lines correspond, respectively, tothe maximum strain in the vessel wall at 120 mmHg, 140 mmHg, and 160mmHg pressure, when no device is placed on the artery. When the devicesherein are placed on the arterial wall, the maximum strain of thearterial wall is increased. Placing the devices on the arterial walltypically reduces the cross-sectional area of the artery. For a givendevice, the more the device compresses the artery, the greater themaximum strain in the arterial walls, and the greater the reduction inthe cross-sectional area of the artery.

The x-axis of the graph of FIG. 11 measures the reduction in thecross-sectional area of the artery generated by the devices. The y-axismeasures the maximum strain in the arterial wall.

It may be observed that for the devices for which the data shown in thegraph was generated, the fewer the number of contact regions that thedevice made with the arterial wall, the more effective the device is atincreasing the maximum strain in the arterial wall for a given reductionin the cross-sectional area of the artery that is caused by the device.For example, by compressing the artery such that it has a 20 percentreduction in its cross-sectional area:

the device having three contact regions generates a maximum increase of75 percent in the arterial wall strain,

the device having four contact regions generates a maximum increase of62 percent in the arterial wall strain,

the device having five contact regions generates a maximum increase of50 percent in the arterial wall strain,

the device having six contact regions generates a maximum increase of 23percent in the arterial wall strain, and

the device having seven contact regions generates a maximum increase ofless than 5 percent in the arterial wall strain.

Thus, in accordance with some applications of the present invention,extravascular devices having three or more contact regions (e.g., threeto six) with the artery are placed around the outside of the artery. Thedevices typically provide contact regions and non-contact regions of thearterial wall, as described hereinabove. The devices typically increasethe strain in the arterial wall, thereby generating increasedbaroreceptor firing in the artery.

Reference is now made to FIG. 12, which is a schematic illustration of adevice 110 that is used to test the baroreceptor response of a subjectto a range of intravascular pressures, in accordance with someapplications of the present invention. For some applications, before anintravascular device is inserted into a subject's artery, thebaroreceptor response of the subject is tested using measuring device110. Catheter 112 is inserted into artery 20, in which the intravasculardevice will be implanted. Extendable arms 114 are extendable from thedistal end of the catheter, and are configured such that the pressurethat the arms exert on the arterial wall increases, as the portion ofthe arms that extends from the catheter increases.

Extendable arms 114 are extended incrementally from the distal end ofthe catheter. At each of the increments, the subject's blood pressure ismeasured in order to determine the baroreceptor response to the pressurethat the arms are exerting on the arterial wall. On the basis of theblood pressure measurements, it is determined which intravascular deviceshould be inserted into the subject's artery, and/or what dimensions theintravascular device should have.

For some applications, a measuring device including arms 114 or asimilar measuring device is left in place in the artery, but catheter112 is removed before the blood pressure measurements are taken. Forexample, the catheter may be removed in order to increase blood flowthrough the artery, relative to when the catheter is in place. Once ithas been determined, using the measuring device, which intravasculardevice should be placed inside the artery, and/or what dimensions theintravascular device should have, the measuring device is removed fromthe artery and the intravascular device is placed inside the artery.

For some applications, a toroid balloon is placed inside the artery andis used as a measuring device. The balloon is inflated incrementallysuch that the balloon applies varying amounts of pressure to thearterial wall, and the subject's blood pressure is measured in order tomeasure the response to the pressure being applied to the wall. In thismanner, it is determined which intravascular device should be used,and/or what dimensions the intravascular device should have. During theaforementioned measuring procedure, blood continues to flow through theartery, via a central hole in the toroid balloon.

For some applications, the intravascular devices described herein areinserted to an implantation site inside or (using a non-transvascularroute) outside of the subject's artery, while the device is in a firstconfiguration thereof. When the device has been placed at theimplantation site, the configuration of the device is changed to asecond configuration, in which the device is effective to increasebaroreceptor stimulation, in accordance with the techniques describedherein. For example, the device may be made of nitinol, or another shapememory material, and the configuration of the device may be changed byapplying an RF signal, and/or another form of energy, to the device. Forsome applications, the device is implanted at an implantation site thatis close to the subject's skin, and the RF signal is applied to thedevice via the subject's skin.

For some applications, devices are applied to the carotid artery of asubject who suffers from carotid sinus hypersensitivity, in order toreduce baroreceptor sensitivity of the carotid sinus, by reducingpulsation of the artery. For example, a device may be placed inside oroutside the artery such that the device makes contact with the artery atmore than six contact points, and/or over more than 180 degrees of thecircumference of the artery. For some applications, a device (e.g., astent) is placed inside or outside of the artery such that the devicemakes 270-360 degrees of contact with the artery.

Reference is now made to FIG. 13, which is a graph showing bloodpressure measured in a dog, before, during and after the bilateralplacement of intravascular devices into the dog's carotid sinuses, inaccordance with some applications of the present invention.Intravascular devices which made contact with the carotid sinus at fourcontact regions (the devices being generally as shown in FIGS. 7A-B)were placed in the dog's left and right carotid sinuses. The beginningand end of the implantation period is indicated in FIG. 13 by,respectively, the left and right vertical dashed lines at about fiveminutes and 153 minutes.

It may be observed that the implantation of the devices in both sinusesresulted in the dog's systolic blood pressure dropping from above 120mmHg to below 80 mmHg, and in the dog's diastolic blood pressuredropping from about 60 mmHg to about 40 mmHg. During the implantationprocedure the dog's blood pressure rose. The inventors hypothesize thatthe rise in blood pressure is due to catheters blocking the flow ofblood to the carotid arteries during the implantation, resulting inreduced baroreceptor stimulation during the implantation procedure. Itis noted that the placement of the device in the dog's sinuses did nothave a substantial effect in the dog's heart rate.

Reference is now made to FIG. 14, which is a graph showing thepressure-strain curve of an artery of a normal subject, a hypertensivesubject, and a hypertensive subject who uses one of the devicesdescribed herein. One of the causes of hypertension is that the arterialwall of the subject does not experience as much strain at any givenpressure, as the arterial wall of a normal subject. Thus, thepressure-strain curve of the hypertensive subject is flattened withrespect to that of a healthy subject and the strain response is shiftedto higher pressures.

The devices described herein increase the strain in the arterial wall atall pressure levels within the artery. For some applications, as shown,at increasing arterial pressures, the absolute increase in the strain inthe arterial wall caused by the device increases, relative to the strainexperienced by the hypertensive subject before implantation of thedevice. Thus, the devices described herein both shift thepressure-strain curve of a hypertensive subject upwards and increase thegradient of the curve. A device is typically selected such that thesubject's pressure-strain curve, subsequent to implantation of thedevice, will intersect the normal pressure-strain curve at a pressure ofbetween 80 mmHg and 240 mmHg.

Reference is now made to FIGS. 15A-B, which are schematic illustrationsof a device 120 for placing in artery 20, in accordance with someapplications of the present invention. Device 120 is generally similarto the intra-arterial devices described hereinabove, except for thedifferences described hereinbelow. FIG. 15A shows a three-dimensionalview of device 120, as the device is shaped when the device is insidethe artery, and FIG. 15B shows a flattened, opened, profile of device120. Device 120 is generally similar to device 80 described hereinabovewith reference to FIGS. 7A-B. Device 120 contacts the wall of the arteryat four contact regions 122 (which comprise strut portions), therebyflattening the non-contact regions of the artery that are between thecontact regions. For some applications, device 120 includes radiopaquemarkers 126 at proximal and distal ends of the device (as shown) or atother portions of the device.

As shown in FIG. 15B, each of the strut portions is generally spacedfrom its two adjacent strut portions by respective distances D1 and D2,D1 being smaller than D2. Thus, the device defines a first set of twosides 124A, having widths D1, and a second set of two sides 124B, havingwidths D2. Placement of device 120 inside artery typically results inthe artery having a cross-sectional shape that is more rectangular thanin the absence of the device, the cross-sectional shape having sideswith lengths D1 and D2. Each of the sides of the cross-sectional shapeis supported by a respective side 124A or 124B of device 120. Typically,the ratio of distance D2 to distance D1 is greater than 1:1, e.g.,greater than 2:1, and/or less than 5:1, e.g., between 1.1:1 and 5:1(e.g., between 1.5:1 and 3:1).

Typically, at the distal and proximal ends of device 120, the device isshaped to define crimping arches 125. During transcatheteral insertionof the device into the subject's artery, the device is crimped about thecrimping arches, such that the span of the device is reduced relative tothe span of the device in its expanded state. Upon emerging from thedistal end of the catheter, the device expands against the arterialwall.

For some applications, each crimping arch 125 has a radius of curvaturer that is less than 6 mm (e.g., less than 1 mm), in order to facilitatecrimping of device 120 about the crimping arch. For some applications,each crimping arch has a radius of curvature r that is greater than 0.3mm, since a crimping arch having a smaller radius of curvature maydamage the arterial wall. Furthermore, when the expanded device exertspressure on the arterial wall, much of the pressure that is exerted onthe device by the arterial wall is resisted by the crimping arches.Therefore, for some applications, each crimping arch has a radius ofcurvature that is greater than 0.3 mm, in order to facilitate resistanceto the pressure that is exerted on the device at the crimping arches.Therefore, for some applications, each crimping arch has a radius ofcurvature that is 0.3-0.6 mm.

For some applications, the thickness of the struts of device 120 at thecrimping arches is greater than the thickness of the struts at otherportions of the device, in order to facilitate resistance to thepressure that is exerted on the device at the crimping arches. For someapplications, there are additional regions of the struts that aresusceptible to absorbing much of the pressure that is exerted on thedevice by the arterial wall, and the thickness of the struts at theadditional regions is greater than the thickness of the struts at otherportions of the device.

Typically, the strut portions of device 120 project outwardly fromcrimping arch 125 at an angle theta, angle theta being greater than 30degrees, e.g., greater than 60 degrees, or greater than 75 degrees.Typically, the outward projection of the struts from the crimping archat such an angle reduces the moment that the arterial wall exerts aboutthe crimping arch, relative to if the struts projected outwardly fromthe crimping arch at a smaller angle. This is demonstrated withreference to FIGS. 15C-D, which show a force F of the arterial wallbeing exerted on struts that project outwardly, respectively, at anglesof alpha and beta, alpha being greater than beta. In FIG. 15C, the forceis exerted on the strut at a distance d1 from the crimping arch, and inFIG. 15D, the force is exerted on the strut at a distance d2 from thecrimping arch, d1 being less than d2. Therefore, the moment that isexerted about crimping point 125 for the strut shown in FIG. 15C is lessthan that of FIG. 15D.

Reference is now made to FIGS. 16A-D, which are schematic illustrationsof another device 130 for placing in artery 20, in accordance with someapplications of the present invention. Device 130 is generally similarto the intra-arterial devices described hereinabove, except for thedifferences described hereinbelow. FIGS. 16B-D show device 130 duringthe shaping of the device, the device typically being placed on ashaping mandrel 132 during the shaping process. As shown, thecross-sectional shape of intra-arterial device 130 varies along thelongitudinal axis of the device. Typically, the device defines strutportions 134, all of which diverge from each other, from a first end ofthe device to the second end of the device. For some applications, eachstrut portion includes two or more parallel struts, as describedhereinbelow.

As shown in FIGS. 16C-D, device 130 is shaped such that at the secondend of the device, the device has a greater span S2, than the span ofthe device S1 at the first end of the device. Typically, the ratio of S2to S1 is greater than 1:1, e.g., greater than 1.1:1, and/or less than2:1, e.g., between 1.1:1 and 2:1 (e.g., between 1.1:1 and 1.4:1).

For some applications, devices are inserted into a subject's artery thatare shaped differently from device 130, but which are also shaped suchthat at the second end of the device, the device has a greater span S2,than the span of the device S1 at the first end of the device, forexample, as described with reference to FIGS. 18A-D.

Due to the ratio of S2 to S1, upon placement of device 130 inside theartery, the shape of the artery typically becomes increasinglynon-circular (e.g., elliptical or rectangular), along the length of theartery, from the first end of the device (having span S1) to the secondend of the device (having span S2). Furthermore, due to the ratio of S2to S1, upon placement of device 130 inside the artery, thecross-sectional area of the artery typically increases along the lengthof the artery, from the first end of the device (having span S1) to thesecond end of the device (having span S2). Typically, the device isplaced such that the first end of the device (which has the smallerspan) is disposed within the internal carotid artery, and the second endof the device (which has the greater span) is disposed at the carotidsinus. In this configuration, the device thus stretches the carotidsinus, due to the span of the device at the second end of the device,but does not substantially stretch the internal carotid artery.

As shown in FIGS. 16C-D, device 130 is shaped such that in the vicinityof the second end of the device, the device has a greater span S2 in afirst direction than a span S3 of the device in a second direction. Forsome applications, the ratio of S2 to S3 is greater than 1:1, e.g.,greater than 2:1, and/or less than 5:1, e.g., between 1.1:1 and 5:1(e.g., between 1.5:1 and 3:1). Typically, the ratio of S2 to S3 enhancesflattening of the artery in which device 130 is placed in the directionof span S2.

Typically, device 130 includes three or more diverging strut portions134, e.g., four diverging strut portions, as shown. For someapplications, device 130 includes crimping arches 125 at the ends of thedevice, the crimping arches being generally similar to crimping arches125, as described hereinabove with reference to device 120. For someapplications, the strut portions of device 130 project outwardly fromcrimping arches 125 at an angle theta, angle theta being greater than 30degrees, e.g., greater than 60 degrees, or greater than 75 degrees, in agenerally similar manner to that described with reference to device 120.For some applications, each of the strut portions comprises two strutsthat are translated longitudinally with respect to one another (i.e.,the struts are doubled), in order to provide mechanical strength to thestruts. Alternatively, each strut portion includes a single strut, ormore than two struts that are translated longitudinally with respect toeach other.

Reference is now made to FIGS. 17A-D, which are schematic illustrationsof yet another device 140 for placing in artery 20, in accordance withsome applications of the present invention. Device 140 is generallysimilar to the intra-arterial devices described hereinabove, except forthe differences described hereinbelow. FIG. 17A shows device 140 duringthe shaping of the device, the device typically being placed on shapingmandrel 132 during the shaping process. As shown, the cross-sectionalshape of intra-arterial device 140 varies along the longitudinal axis ofthe device.

As shown in FIG. 17B, device 140 is shaped such that at the second endof the device, the device has a greater span S2, than the span of thedevice S1 at the first end of the device. Typically, the ratio of S2 toS1 is greater than 1:1, e.g., e.g., greater than 1.1:1, and/or less than2:1, e.g., between 1.1:1 and 2:1 (e.g., between 1.1:1 and 1.4:1).

Due to the ratio of S2 to S1, upon placement of device 140 inside theartery, the shape of the artery typically becomes increasinglynon-circular (e.g., elliptical or rectangular), along the length of theartery, from the first end of the device (having span S1) to the secondend of the device (having span S2). Furthermore, due to the ratio of S2to S1, upon placement of device 130 inside the artery, thecross-sectional area of the artery typically increases along the lengthof the artery, from the first end of the device (having span S1) to thesecond end of the device (having span S2). Typically, the device isplaced such that the first end of the device (which has the smallerspan) is disposed within the internal carotid, and the second end of thedevice (which has the greater span) is disposed at the carotid sinus. Inthis configuration, the device thus stretches the carotid sinus, due tothe span of the device at the second end of the device, but does notsubstantially stretch the internal carotid.

Device 140 is shaped to define four sides. Two of the sides, which areopposite to one another, are configured to act as artery contact regions142 (shown in FIG. 17C), and apply pressure to the walls of the arteryby contacting the artery. The other two sides of device 140, which arealso opposite to one another, are configured to act as crimping regions144 (shown in FIG. 17D). During transcatheteral implantation of thedevice into the artery, the crimping regions facilitate crimping of thedevice.

It is noted that the sides of device 140 that act as artery contactregions 142 are typically also somewhat crimpable. Typically, as shown,the sides of device 140 that act as artery contact regions 142 includecrimping arches 125 (as described hereinabove), which facilitatecrimping of the device.

An artery contacting region 142 of device 140 is shown in FIG. 17C. Uponimplantation inside an artery, artery contact regions 142 exert pressureon the artery wall, thereby flattening regions of the arterial wallbetween the artery contact regions, and increasing the strain in thearterial wall at the flattened regions, as described hereinabove. Forsome applications, the artery contact regions comprise two or morestruts 146 that are translated longitudinally with respect to oneanother. Typically, the struts of a given artery contact region arecoupled to one another by a reinforcing element 148. For someapplications, the reinforcing element is disposed such that when theartery contact region is crimped, the longitudinal translation of thestruts with respect to one another is maintained. For some applications,struts 146 of device 140 project outwardly from crimping arches 125 atan angle theta, angle theta being greater than 30 degrees, e.g., greaterthan 60 degrees, or greater than 75 degrees, in a generally similarmanner to that described with reference to device 120.

A crimping region 144 of device 140 is shown in FIG. 17D. For someapplications, crimping region 144 comprises a locking mechanism 149.During crimping of the device, the locking mechanism is unlocked, tofacilitate crimping of the device. When the device is implanted intoartery 20, the locking mechanism is locked, so as to prevent thecrimping regions from becoming crimped due to pressure that is exertedon the device by the artery. For example, the locking mechanism maycomprise two struts 150 that are shaped so as to become locked in placedwith respect to one another at a locking interface 152. In order tocrimp the device, one of the struts is forced above or below the planeof the locking interface. The struts are pre-shaped, such that when thestruts are not locked with respect to one another, the struts movetoward one another, such that the struts at least partially overlap withone another. Alternatively or additionally, other locking mechanisms areused. For example, a hinged-based mechanism may be used.

Reference is now made to FIGS. 18A-B, which are schematic illustrationsof respective sides 124A and 124B of device 120 for placing in artery20, in accordance with some applications of the present invention.Device 120 is generally as described hereinabove with reference to FIGS.15A-B, except that device 120 as shown in FIGS. 18A-B is shaped suchthat at the second end of the device, the device has a greater span S2,than the span of the device S1 at the first end of the device.Typically, the ratio of S2 to S1 is greater than 1:1, e.g., e.g.,greater than 1.1:1, and/or less than 2:1, e.g., between 1.1:1 and 2:1(e.g., between 1.1:1 and 1.4:1).

Reference is now made to FIGS. 18C-D, which are schematic illustrationsof respective sides 124A and 124B of device 120 for placing in artery20, in accordance with some applications of the present invention.Device 120 is generally as described hereinabove with reference to FIGS.15A-B and FIGS. 18A-B, except that device 120 as shown in FIGS. 18C-D isshaped such that (a) sides 124A and 124B are of equal widths, and (b) atthe second end of the device, the device has a greater span S2, than thespan of the device S1 at the first end of the device. For someapplications, a device is used that defines four parallel artery contactregions 122, all of which are separated from adjacent artery contactregions by an equal distance, as shown in FIGS. 18C-D.

Typically, the ratio of S2 to S1 of device 120 as shown in FIGS. 18C-Dis as described hereinabove. Thus, the ratio of S2 to S1 is typicallygreater than 1:1, e.g., e.g., greater than 1.1:1, and/or less than 2:1,e.g., between 1.1:1 and 2:1 (e.g., between 1.1:1 and 1.4:1).

Reference is now made to FIG. 19, which is a schematic illustration of aD-shaped device 150 for placing inside artery 20, in accordance withsome applications of the present invention. For some applications, adevice having a D-shaped cross-section, as shown, is placed inside theartery. A straight portion 152 of the cross-sectional shape flattens aportion of the arterial wall that is adjacent to the straight portion,thereby increasing the strain in the portion of the arterial wallrelative to the strain in the portion of the arterial wall in theabsence of the device.

It is noted that device 120 and other intra-arterial devices describedherein (such as devices 70, 80, and 90) define contact regions thatcontact the intra-arterial wall, the contact regions comprising aplurality of generally parallel strut portions. Typically, for each ofthe devices, the minimum distance between a first strut portion of thedevice and an adjacent strut portion to the first strut portion, is 2mm. It is further noted that the intra-arterial devices described herein(such as devices 60, 70, 80, 90, 120, 130, 140, and 150) cause theartery to assume a non-circular cross-sectional shape, such as atriangular, a rectangular, or an oval shape.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and 150) are shaped to definestruts, or other artery contact regions, that are configured to change ashape of the arterial wall, by exerting a force on the arterial wall.The devices additionally include a mesh in between the regions that areconfigured to change the shape of the arterial wall. The mesh isconfigured not to change the mechanical behavior of the artery (e.g., bychanging the shape of the arterial wall), but is configured to preventstrokes caused by embolization of arterial plaque, by stabilizing thearterial plaque, in a generally similar manner to a regular stent. Ingeneral, for some applications, the intra-arterial described herein areused to treat hypertension, and are additionally used to treat arterialdisease. For some applications, the intra-arterial devices describedherein are placed in a subject's carotid artery subsequent to, orduring, a carotid endarterectomy procedure.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and 150) are configured, uponimplantation of the device inside the artery, to cause one or morecontiguous portions of the arterial wall to become flattened, each ofthe contiguous portions having an area of more than 10% of the totalsurface area of the artery in the region in which the device is placed.Typically, the aforementioned devices contact less than 20 percent(e.g., less than 10 percent) of the wall of the artery at anylongitudinal location along the artery. As described hereinabove, forsome applications, the intravascular devices described herein (such asdevices 60, 70, 80, 90, 120, 130, 140, and 150) have a totalcross-sectional area of less than 5 sq mm, e.g., less than 0.8 sq mm, orless than 0.5 sq mm. (The total cross-sectional area should beunderstood to refer to the cross-sectional area of the solid portions ofthe devices, and not the space in between the solid portions.) Thedevices typically have this cross-sectional area over a length of thedevice of more than 4 mm, e.g., more than 6 mm, and/or less than 12 mm,e.g. less than 10 mm. For example, the devices may have theaforementioned cross sectional area over a length of 4 mm-12 mm, e.g., 6mm-10 mm, or over a length of 10 mm-30 mm.

For some applications, the dimensions of the intra-arterial devicesdescribed herein (such as devices 60, 70, 80, 90, 120, 130, 140, and150) are chosen based upon patient-specific parameters.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and/or 150) are made of ashape-memory alloy, such as nitinol. The nitinol is configured to assumean open, deployed configuration at body temperature, and to assume acrimped configuration in response to being heated or cooled to atemperature that differs from body temperature by a given amount, suchas by 5 C. In order to insert the device, the device is heated orcooled, so that the device assumes its crimped configuration. The deviceis placed inside the artery, and upon assuming body temperature (or atemperature that is similar to body temperature), the device assumes itsdeployed, open configuration. Subsequently, the device is retrieved fromthe artery by locally heating or cooling the region of the artery inwhich the device is disposed. The device assumes its crimpedconfiguration and is retrieved from the artery using a retrieval device.For some applications, a device is inserted into the artery temporarilyin order to cause the artery to undergo a permanent shape change.Subsequent to changing the shape of the artery, the device is retrievedfrom the artery, for example, in accordance with the techniquesdescribed above.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and/or 150) are configured toexpand both radially and longitudinally upon implantation of the deviceinside the subject's artery.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and/or 150) are implanted at asubject's carotid bifurcation, via a delivery device. During theimplantation of the device, the proximal end of the device is releasedfrom the delivery device such that the proximal end of the device ispositioned at the start of the bifurcation. Subsequent to the proximalend of the device having been positioned, the distal end of theintravascular device is released from the delivery device. For someapplications, prior to releasing the distal end of the device, theeffect of the device on baroreceptor firing is measured, and theposition of the device is adjusted, in response thereto.

For some applications, the intra-arterial devices described herein (suchas devices 60, 70, 80, 90, 120, 130, 140, and/or 150) are configuredsuch that, upon implantation of the device inside artery 20, the shapeof the device remains substantially the same for the duration of acardiac cycle of the subject. Alternatively, the device is configured toflex in response to the subject's cardiac cycle. For some applicationsthe device flexes passively, in response to blood pressure changes inthe artery. Alternatively or additionally, the device is activelyflexed. For example, the device may include a piezoelectric element, andan inductive charged coil (inside or outside of the subject's body),drives the piezoelectric element to flex.

For some applications, baroreceptors of the subject are activated bydriving an electrical current toward the baroreceptors via anintra-arterial device described herein (such as device 60, 70, 80, 90,120, 130, 140, and/or 150). Thus, the baroreceptors are stimulated bothby mechanical shape changes to the artery as a result of the devicebeing placed inside the artery, and via the electrical stimulation ofthe baroreceptors. For some applications, baroreceptors at leastpartially adapt to the shape change of the artery due to the placementof intra-arterial device inside the artery, and the baroreceptors firewith a lower firing rate at a given blood pressure, relative to when thedevice was first implanted. For some applications, in response to thelowered firing rate of the baroreceptors, due to the adaptation of thebaroreceptors to the implanted device, electrical stimulation of thebaroreceptors is increased.

Reference is made to FIG. 20, which is a graph showing the derivative ofstrain versus pressure as a function of rotational position around theartery, in accordance with respective models of an artery, in accordancewith some applications of the present invention. The graph shows thederivative of strain versus pressure as a function of rotationalposition around a quadrant of an artery, for the following four modelsof the artery:

1) A circular elastic artery having no device placed therein, at 150mmHg.

2) An artery having device 120 placed therein, the device causing theartery to assume a rectangular shape. The artery is modeled at apressure of 150 mmHg. One of the contact points of the device with theartery wall is between 40 and 80 arbitrary units along the x-axis.

3) A rectangular artery without a device placed therein, at 80 mmHg. Oneof the corners of the rectangle is at 40 and 80 arbitrary units alongthe x-axis. This model of the artery was generated in order to separatethe effect of changing the shape of the artery to a rectangular shapefrom the effect of having a device (such as device 120) placed insidethe artery.

4) The rectangular artery without a device placed therein, at 150 mmHg.

The shapes of the curves indicate the following:

1) As expected, the derivative of the strain with respect to pressure ofthe circular, elastic artery is constant due to the elasticity of theartery.

2) At the contact point of the intra-arterial device with the artery,the strain-pressure derivative is reduced relative to the roundedartery. At the non-contact regions of the artery, the strain-pressurederivative is also reduced relative to the rounded artery. However, atthe non-contact regions, the pressure-strain derivative is stillapproximately half that of the rounded artery. This indicates that atthe non-contact regions, the pulsatility of the artery is reduced,relative to a rounded artery, but that the artery is still substantiallypulsatile. Therefore, for some applications, devices are inserted intoan artery which re-shape the arterial wall, such that at anylongitudinal point along the artery there are non-contact regions atwhich regions there is no contact between the device and the arterialwall, such that the artery is able to pulsate.

3) Based on the two rectangular models of the artery (at 80 mmHg and 150mmHg), it may be observed that at the straightened regions of the artery(i.e., not at the corner of the rectangle), the strain-pressurederivative of the artery increases at low-pressures (e.g., 80 mmHg),relative to a rounded, elastic artery. At higher pressures (e.g., 150mmHg), the strain-pressure derivative of the straightened regions of theartery is roughly equal to that of the rounded, elastic artery. Thisindicates that straightening the wall of the artery, by causing theartery to assume a rectangular or an elliptical shape, may increase thepulsatility of the artery. Therefore, for some applications, devices areinserted into the artery that straighten regions of the arterial wall.

Experimental Data

A number of experiments were conducted by the inventors in accordancewith the techniques described herein.

In one experiment, acute unilateral carotid stimulation was applied to afirst set of dogs, either the left or right carotid sinus of the dogs ofthe first set being squeezed between two smooth metal plates for aperiod of two to five minutes. Acute bilateral carotid stimulation wasapplied to a second set of dogs, both carotid sinuses of the dogs of thesecond set being squeezed between two smooth metal plates for a periodof 10 to 30 minutes. The mean effect of the unilateral carotid sinusstimulation was to decrease systolic blood pressure by 11 mmHg, and themean effect of the bilateral stimulation was to decrease systolic bloodpressure by 29 mmHg. The results of the bilateral stimulation had ap-value of less than 0.001. These results indicate that using thedevices described herein for either unilateral or for bilateral carotidsinus stimulation may be effective at reducing a subject's bloodpressure.

In another experiment, two dogs were chronically implanted (for periodsof more than two months) with plates that squeezed the carotid sinus, inaccordance with the techniques described herein. The dogs had the platesimplanted around both carotid sinuses. On a first one of the dogs, theplates became dislodged from one of the sinuses within two days ofimplantation. The plates remained implanted around both carotid sinusesof the second dog, until the plates were removed. The blood pressure ofthe dogs was measured, via an implanted telemeter, for two to four weeksbefore the device implantation. In the first dog, the dog's bloodpressure was measured after the implantation of the device for twoweeks, and was subsequently terminated, due to a malfunction in thetransmission of the telemeter. In the second dog, the dog's bloodpressure was measured for six weeks after the implantation of thedevice.

For the dog that had the plates chronically implanted around only onecarotid sinus, the average diastolic blood pressure measured in the dogover two weeks post-implantation was 6 mmHg less than the averagediastolic blood pressure measured in the dog over two weekspre-implantation. The average systolic blood pressure measured in thedog over two weeks post-implantation was 8 mmHg less than the averagesystolic blood pressure measured in the dog over two weekspre-implantation.

For the dog that had the plates chronically implanted bilaterally, theaverage diastolic blood pressure measured in the dog over six weekspost-implantation was 10 mmHg less than the average diastolic bloodpressure measured in the dog over two weeks pre-implantation. Theaverage systolic blood pressure measured in the dog over six weekspost-implantation was 18 mmHg less than the average systolic bloodpressure measured in the dog over two weeks pre-implantation.

These results indicate that chronic implantation of the devicesdescribed herein for either unilateral or for bilateral carotid sinusstimulation may be effective at chronically reducing a subject's bloodpressure.

In addition to measuring the blood pressure of the dog that had plateschronically implanted bilaterally around its carotid sinuses, theinventors measured the baroreceptor sensitivity of the dog, for severalweeks, both pre-implantation and post-implantation of the device usinggenerally similar techniques to those described in “The effect ofbaroreceptor activity on cardiovascular regulation,” by Davos (HellenicJ Cardiol 43: 145-155, 2002), which is incorporated herein by reference.Pre-implantation of the device, the mean baroreceptor sensitivity was14±5 sec/mmHg. Post-implantation of the device, the mean baroreceptorsensitivity was 20±8 sec/mmHg. These results indicate that chronicimplantation of the devices described herein may be effective atincreasing baroreceptor sensitivity.

In a further experiment that was conducted in accordance with thetechniques described herein, five human patients had a device placedaround either the left or right carotid sinus, subsequent to undergoingendarterectomy procedures. The device was configured to flatten regionsof the wall of the carotid sinus, in accordance with techniquesdescribed herein. Of the five patients, two were excluded from thestudy, since these patients were administered atropine, which may haveinterfered with the results. Of the three patients who were included inthe study, the placement of the device in all of the patients resultedin a decrease in both the systolic and diastolic blood pressure of thepatient. For the three patients who were included in the study, theplacement of the device resulted in a mean decrease in diastolic bloodpressure of 8 mmHg (standard deviation 5) and a mean decrease insystolic blood pressure of 22 mmHg (standard deviation 14), relative tothe blood pressures before placement of the device. These resultsindicate that using the devices described herein for carotid sinusstimulation may be effective at reducing a human subject's bloodpressure.

The scope of the present invention includes combining the apparatus andmethods described herein with those described in US 2008/0033501 toGross, and/or U.S. patent application Ser. No. 12/602,787 to Gross, bothof which applications are incorporated herein by reference.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

What is claimed is:
 1. Apparatus, comprising: an implantable devicehaving four artery-contacting strut portions, the implantable devicedefining a polygonal cross-section from a proximal end thereof to adistal end thereof with the artery-contacting strut portions beingvertices thereof, wherein the artery-contacting strut portions areparallel to each other, wherein the implantable device is configured tochange a shape of a blood vessel when placed therein, and wherein, whenthe implantable device is in a fully expanded configuration, each of theartery-contacting strut portions are disposed at a first distance from afirst directly circumferentially adjacent artery-contacting strutportion, and at a second distance from a second directlycircumferentially adjacent artery-contacting strut portion, the seconddistance being greater than the first distance.
 2. The apparatusaccording to claim 1, wherein a ratio of the second distance to thefirst distance is between 1.1:1 and 5:1.
 3. The apparatus according toclaim 2, wherein the ratio of the second distance to the first distanceis between 1.5:1 and 3:1.